Vitamin B12 Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin B12, including details on cyanocobalamin, benefits, supplements, deficiency, side-effects, sources.

Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death.

Hemendinger RA, Armstrong EJ, Brooks BR

Motor Neuron Cell Biology Group, Department of Neurology, Carolinas Neuromuscular/ALS-MDA Center, Carolinas Medical Center, Charlotte, NC 28203, USA. richelle.hemendinger@carolinashealthcare.org

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC₅₀ (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, confirmed by activation of caspase 3/7. Induction of apoptosis was independent of short-term reactive oxygen species (ROS) generation. Methyl Vitamin B12 (MeCbl) and methyl tetrahydrofolate (MTHF), used clinically to treat elevated homocysteine levels, were tested for their ability to reverse homocysteine-mediated motor neuron cell death. MeCbl in the micromolar range was able to provide neuroprotection (2 h pretreatment prior to homocysteine) and neurorescue (simultaneous exposure with homocysteine) against millimolar homocysteine with an IC₅₀ (concentration at which 50% of maximal cell death is inhibited) of 0.6 μM and 0.4 μM, respectively. In contrast, MTHF (up to 10 μM) had no effect on homocysteine-mediated cell death. MeCbl inhibited caspase 3/7 activation by homocysteine in a time- and dose-dependent manner, whereas MTHF had no effect. We conclude that MeCbl is effective against homocysteine-induced cell death in motor neurons in a ROS-independent manner, via a reduction in caspase activation and apoptosis. MeCbl decreases Hcy induced motor neuron death in vitro in a hybrid cell line derived from motor neuron-neuroblastoma and may play a role in the treatment of late stage ALS where HCy levels are increased in animal models of ALS.

Published 1 March 2011 in Toxicol Appl Pharmacol, 251(3): 217-25.
Full-text of this article is available online (may require subscription).

Articles on Vitamin B12 published 1 March 2011:

Methyl Vitamin B12 but not methylfolate rescues a motor neuron-like cell line from homocysteine-mediated cell death.   Toxicol Appl Pharmacol, 251(3): 217-25.

Homocysteine is an excitatory amino acid implicated in multiple diseases including amyotrophic lateral sclerosis (ALS). Information on the toxicity of homocysteine in motor neurons is limited and few studies have examined how this toxicity can be modulated. In NSC-34D cells (a hybrid cell line derived from motor neuron-neuroblastoma), homocysteine induces apoptotic cell death in the millimolar range with a TC₅₀ (toxic concentration at which 50% of maximal cell death is achieved) of 2.2 mM, ... [Abstract] [Full-text]

Articles on Vitamin B12 published 21 February 2011:

Unexplained chronic cough and vitamin B-12 deficiency.   Am J Clin Nutr, 93(3): 542-8.

[Abstract] [Full-text]

Articles on Vitamin B12 published 5 January 2011:

Evolution in a family of chelatases facilitated by the introduction of active site asymmetry and protein oligomerization.   Proc Natl Acad Sci U S A, 108(1): 97-102.

The class II chelatases associated with heme, siroheme, and cobalamin biosynthesis are structurally related enzymes that insert a specific metal ion (Fe(2+) or Co(2+)) into the center of a modified tetrapyrrole (protoporphyrin or sirohydrochlorin). The structures of two related class II enzymes, CbiX(S) from Archaeoglobus fulgidus and CbiK from Salmonella enterica, that are responsible for the insertion of cobalt along the cobalamin biosynthesis pathway are presented in complex with their ... [Abstract] [Full-text]

Articles on Vitamin B12 published 21 December 2010:

Contributions of enriched cereal-grain products, ready-to-eat cereals, and supplements to folic acid and vitamin B-12 usual intake and folate and vitamin B-12 status in US children: National Health and Nutrition Examination Survey (NHANES), 2003-2006.   Am J Clin Nutr, 93(1): 172-85.

[Abstract] [Full-text]

Articles on Vitamin B12 published 1 December 2010:

Most harmful algal bloom species are vitamin B1 and B12 auxotrophs.   Proc Natl Acad Sci U S A, 107(48): 20756-61.

Eutrophication can play a central role in promoting harmful algal blooms (HABs), and therefore many HAB studies to date have focused on macronutrients (N, P, Si). Although a majority of algal species require exogenous B vitamins (i.e., auxotrophic for B vitamins), the possible importance of organic micronutrients such as B vitamins (B(1), B(7), B(12)) in regulating HABs has rarely been considered. Prior investigations of vitamins and algae have examined a relatively small number of ... [Abstract] [Full-text]

Articles on Vitamin B12 published 29 November 2010:

Structures of the human GTPase MMAA and vitamin B12-dependent methylmalonyl-CoA mutase and insight into their complex formation.   J Biol Chem, 285(49): 38204-13.

Vitamin B(12) (cobalamin, Cbl) is essential to the function of two human enzymes, methionine synthase (MS) and methylmalonyl-CoA mutase (MUT). The conversion of dietary Cbl to its cofactor forms, methyl-Cbl (MeCbl) for MS and adenosyl-Cbl (AdoCbl) for MUT, located in the cytosol and mitochondria, respectively, requires a complex pathway of intracellular processing and trafficking. One of the processing proteins, MMAA (methylmalonic aciduria type A), is implicated in the mitochondrial assembly ... [Abstract] [Full-text]

Articles on Vitamin B12 published 26 November 2010:

Age-related hearing loss, vitamin B12, and folate in the elderly.   Otolaryngol Head Neck Surg, 143(6): 826-30.

[Abstract] [Full-text]

Articles on Vitamin B12 published 22 November 2010:

Vitamin B12-responsive severe leukoencephalopathy and autonomic dysfunction in a patient with "normal" serum B12 levels.   J Neurol Neurosurg Psychiatry, 81(12): 1369-71.

Leukoencephalopathy and autonomic dysfunction have been described in individuals with very low serum B(12) levels (<200 pg/ml), in addition to psychiatric changes, neuropathy, dementia and subacute combined degeneration. Elevated homocysteine and methylmalonic acid levels are considered more sensitive and specific for evaluating truly functional B(12) deficiency. A previously healthy 62-year-old woman developed depression and cognitive deficits with autonomic dysfunction that progressed over ... [Abstract] [Full-text]

© 2004-2011 Vitamin B12 Research Today. All Rights Reserved.